title: The presence and prognostic impact of apoptotic and nonapoptotic disseminated tumor cells in the bone marrow of primary breast cancer patients after neoadjuvant chemotherapy.
abstract: BACKGROUND
  Neoadjuvant systemic therapy of primary breast cancer (PBC) patients offers the possibility to monitor treatment response. However, patients might have metastatic relapse despite achieving a pathologic complete response (pCR). This indicates that local response to therapy must not be representative for systemic treatment efficacy. Therefore, the aim of this study was to compare local response with systemic tumor cell dissemination by determining the presence of disseminated tumor cells (DTCs), including apoptotic tumor cells, in the bone marrow (BM) of PBC patients after neoadjuvant chemotherapy (NACT).
  
  
  METHODS
  DTCs were detected by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology (DTC status). The presence of apoptotic tumor cells was determined by using the M30 antibody (M30 status). This antibody detects a neo-epitope that is expressed only during early apoptosis.
  
  
  RESULTS
  BM aspirates from 400 PBC patients that had completed NACT were eligible for this study. Of these, 167 (42%) patients were DTC positive (DTC status). The M30 status was investigated in 308 patients. Apoptotic (M30-positive) tumor cells were detected in 89 (29%) of these. Whereas the DTC status was not correlated (P = 0.557) to local treatment response (that is, pCR or a clinical complete/partial response), the presence of M30-positive tumor cells was significantly higher in patients that responded to therapy (P = 0.026). Additionally, DTC-positive patients were at an increased risk for disease relapse (hazard ratio, 1.87; 95% CI, 1.11 to 3.15; P = 0.019).
  
  
  CONCLUSIONS
  The presence of DTC is independent of therapy response of the primary tumor. As patients that are DTC positive after NACT have an unfavorable outcome, they might benefit from additional systemic treatment.
authors.forename: Andreas Daniel
authors.initials: AD
authors.lastname: Hartkopf
authors.forename: Florin-Andrei
authors.initials: FA
authors.lastname: Taran
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.forename: Carsten
authors.initials: C
authors.lastname: Hagenbeck
authors.forename: Carola
authors.initials: C
authors.lastname: Melcher
authors.forename: Natalia
authors.initials: N
authors.lastname: Krawczyk
authors.forename: Markus
authors.initials: M
authors.lastname: Hahn
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult